Abstract
The specific activity of orotidine 5′-monophosphate (OMP) decarboxylase in cultured human fibroblasts is an exponential function of the concentration of cell protein in the extract. Low concentrations of uridylic or cytidylic acid augment the catalytic activity of dilute solutions of cell extract but not of concentrated ones. In the presence of urea, specific activity becomes independent of protein concentration, and uridylic or cytidylic acid augments activity over all concentrations of cell extract. These results, as well as other observations, suggest that the decarboxylase may be composed of subunits which are in dynamic equilibrium with an aggregate. At least one of the subunits is likely to have catalytic activity for the reaction, though less activity than the aggregate. The effect of the mutant gene for orotic aciduria on OMP decarboxylase is easily demonstrated when cell extracts are assayed in either the presence or the absence of urea.
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References
Howell, R. R., Klinenberg, J. R., and Krooth, R. S. (1967). Enzyme studies on diploid cell strains developed from patients with hereditary orotic aciduria. Johns Hopkins Med. J. 12081.
Jeffay, H. (1963). Counting C14O2 with a liquid scintillation counter. In Rothschild, S. (ed.), Advances in Tracer Methodology, Vol. 1, Plenum Press, New York, pp. 113–114.
Krooth, R. S. (1964). Properties of diploid cell strains developed from patients with an inherited abnormality of uridine biosynthesis. Cold Spring Harbor Symp. Quant. Biol. 29189.
Krooth, R. S. (1970). Studies bearing on the regulation of uridine-5′-monophosphate biosynthesis in human diploid cells. In Padykula, H. (ed.), Control Mechanisms in Expression of Cellular Phenotypes, Academic Press, New York, pp. 43–68.
Pan, Y. L., and Krooth, R. S. (1968). The influence of progressive growth on the specific activity of human diploid cell strains. I. Effect of cellular genotype: Homozygous strains. J. Cell. Physiol. 77151.
Pinsky, L., and Krooth, R. S. (1967a). Studies on the genetic control of pyrimidine biosynthesis in human diploid cell strains. I. Effect of 6-azauridine on cellular phenotype. Proc. Natl. Acad. Sci. 57925.
Pinsky, L., and Krooth, R. S. (1967b). Studies on the genetic control of pyrimidine biosynthesis in human diploid cell strains. II. Effects of 5-azaorotic acid and pyrimidine precursors on cellular phenotype. Proc. Natl. Acad. Sci. 571267.
Smith, L. H., Sullivan, M., and Huguley, C. M., Jr. (1961). Pyrimidine metabolism in man. IV. Enzymatic defect of orotic aciduria. J. Clin. Invest. 40656.
Smith, L. H., Huguley, C. M., Jr., and Bain, J. A. (1966). Hereditary orotic aciduria. In Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S. (eds.), The Metabolic Basis of Inherited Disease, 2nd ed., McGraw-Hill Book Co., New York, pp. 739–758.
Tomkins, G. M., Yielding, L. K., Talal, N., and Curran, J. F. (1963). Protein structure and biological regulation. Cold Spring Harbor Symp. Quant. Biol. 28461.
Wuu, K. D., and Krooth, R. S. (1968). Dihydroorotic acid dehydrogenase activity of human diploid cell strains. Science 160539.
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Supported by Program Project Grants 1-PO1-GM 15419 and GM 18153-1, National Institutes of Health, United States Public Health Service.
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Krooth, R.S., Pan, YL. & Pinsky, L. Studies of the orotidine 5′-monophosphate decarboxylase activity of crude extracts of human cells. Biochem Genet 8, 133–148 (1973). https://doi.org/10.1007/BF00485541
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DOI: https://doi.org/10.1007/BF00485541